Recently, it is known that the life-style related diseases such as arteriosclerosis, hyperlipemia, diabetes, hypertension, and central obesity, are developed based on a common metabolic abnormality, which has been referred to as a metabolic syndrome. According to the Ordinance of the Ministry of Health, Labour and Welfare No. 157 “Practice guideline for special health checkups and special health-maintenance guidance (Dec. 28, 2007)”, a special health check-up was given to insured persons aged between 40 and 74. Examinations of waist circumference, blood pressure, serum triglyceride (neutral fat) level, high-density lipoprotein cholesterol (HDL-C) level, and blood glucose were carried out from April, 2008. As health guidance is given to the persons diagnosed with metabolic syndrome, health awareness in people has been increased. Thus, it is becoming popular to prevent life-style related disease in a positive manner.
Hitherto, as a risk marker for development of arteriosclerosis, high-density lipoprotein cholesterol (HDL-C) level, low-density lipoprotein cholesterol (LDL-C) level, small, dense LDL (sdLDL), apolipoprotein A, adiponectin, CRP (C-reactive Protein), and AIP (Atherogenic Index of Plasma), and the like are known.
sdLDL is a LDL which contains a high proportion of triglyceride, and has a smaller particle size than normal LDL. sdLDL is more susceptible to oxidation compared to normal LDL, and it is known that sdLDL strongly causes the development of arteriosclerosis. Apolipoprotein A constitutes HDL, and promotes the removal of cholesterol from cells. Adiponectin is a hormone released from adipocyte, and it is known that adiponectin exhibits functions to promote insulin sensitivity, prevent arteriosclerosis, and inhibit inflammation. Further, the blood concentration of adiponectin is negatively correlated with the amount of visceral fat. CRP is produced when an inflammatory reaction is developed in the body. CRP has attracted attention as a marker of arteriosclerosis with a chronic vascular inflammation. AIP is an index in serum for arteriosclerosis which is calculated by a formula, “log (triglyceride concentration/HDL-C concentration)”, using a triglyceride concentration and HDL-C concentration.
Further, it is said that oxidation of LDL is the greatest contributor to the development of arteriosclerosis. LDL which is oxidized through abnormalities of metabolism or transport of cholesterol, leads to a conversion of macrophages to foam cells, and induces the production of superoxide from neutrophil, whereby the oxidized LDL further induces lipid peroxidation and lipid accumulation at vascular subendothelium so as to progress arteriosclerosis. Therefore, in order to prevent the development of arteriosclerosis, it is remarkably effective to inhibit the oxidation of LDL.
Plasmalogen is a kind of glycerophospholipid, and has an olefinyl chain (vinyl ether bond) at the sn-1 position, an acyl chain at the sn-2 position, and a base-bound phosphoric acid at the sn-3 position of the glycerol backbone. In the plasmalogen present in a living body, the number of carbon atoms of the major olefinyl chain is 16 to 18, and the major acyl chain is a fatty acid having 16 to 22 carbon atoms. The major base bound to phosphoric acid is choline or ethanolamine, and the corresponding plasmalogens are referred to as choline plasmalogen (hereinafter sometimes referred to as a “CP”) or ethanolamine plasmalogen (hereinafter sometimes referred to as an “EP”), respectively. It is known that the proportion of CP is high in the heart and skeletal muscle of mammals, and a proportion of EP is high in the brain and kidneys of mammals.
The concentration of phospholipids in human plasma is 2 to 3 mM, and the phospholipids are contained therein as a constituent of lipoprotein. 60 to 75% of the total phospholipids are choline glycerophospholipid, 2 to 5% thereof are ethanolamine glycerophospholipid, and 10 to 20% thereof are sphingomyelin phospholipid.
The concentration of plasmalogen in human plasma is 0.1 to 0.3 mM, and proportions of CP and EP are 40% and 60% respectively. That is, about 5% of choline glycerophospholipid and about 60% of ethanolamine glycerophospholipid are plasmalogen, and there are very few plasmalogen having a base other than choline and ethanolamine, in blood.
Reported physiological roles of plasmalogen are: a function of membrane fusion in cell fusion or secretory action, an involvement in signal transduction or transport of biological macromolecule, a role as a reservoir of polyunsaturated fatty acid which is easily oxidized, and a role as an endogenous antioxidant. Further, it is reported that an inherited plasmalogen deficiency in humans exhibits symptoms of profound mental retardation, adrenal disorder, cataracts, hearing disorder, stunted growth, or the like. It is also reported that the serum plasmalogen level in Alzheimer's disease patients and aged persons is decreased. These findings suggest that plasmalogen plays an important role in the body (non-patent literature 1). In addition, it is known that plasmalogen synthesized in liver is preferentially incorporated into lipoprotein component. Furthermore, it is considered that plasmalogen acts as an antioxidative factor for LDL due to the endogenous antioxidant activity thereof.
Patent literature 1 discloses that choline plasmalogen level and ethanolamine plasmalogen level in the blood of persons of middle or advanced age including hyperlipemia patients were measured, and the CP/EP ratio is significantly correlated to fasting triglyceride level, which means the neutral fat level, and LDL size, which means the sdLDL level, respectively (the corresponding correlation coefficients are −0.359 and 0.402 respectively). Further, patent literature 1 discloses that the CP/EP ratio can be used as a biomarker for preventing life-style related disease. In addition, non-patent literature 1 discloses that the amount of total CP or the amount of total EP is correlated to HDL-C, apolipoprotein A-I, and apolipoprotein A-II (the correlation coefficients are more than 0.28).
However, the correlations between the CP/EP ratio and fasting triglyceride (neutral fat) or LDL size (sdLDL), disclosed in patent literature 1; and the correlations between the total CP amount or the total EP amount and HDL-C, apolipoprotein A-I, or apolipoprotein A-II disclosed in non-patent literature 1, are not sufficiently strong, and therefore these biomarkers for detecting life-style related disease are by no means satisfactory.